Biomarker tests for invasive Candida infection in critically ill patients in the UK (A-Stop): a multicentre diagnostic test accuracy study

Why clinicians should know about it

• Picked for Biochemistry (medical) (top studies of the week, 25 October 2026): Large multicentre diagnostic accuracy study of fungal biomarkers
• Picked for Microbiology (medical) (top studies of the week, 25 October 2026): Multicentre diagnostic accuracy assessment of Candida biomarkers in ICU patients

Abstract

BACKGROUND: The current practice of empirical antifungal treatment for suspected invasive Candida infection in the intensive care unit (ICU) leads to overtreatment. Biomarkers might better target treatment; however, their diagnostic accuracy in this patient group is uncertain. This study aimed to evaluate whether a biomarker or a combination of biomarkers has sufficiently high negative predictive value (NPV) to enable early cessation of empirical antifungal treatment in patients in ICUs. METHODS: In this prospective, multicentre, diagnostic test accuracy study, we recruited patients who had been started on empirical antifungal treatment for suspected candidiasis and had blood cultures drawn within 24 h of starting treatment from 43 UK ICUs. We tested a research blood sample, collected within 24 h of the standard-of-care care blood culture (ie, within 48 h of starting empirical antifungal treatment), with three DNA detection tests (Fungiplex, T2Candida, and CandID) and one (1,3)-β-D-glucan test (Fungitell). We assessed the accuracy of these tests against an international consensus definition of proven invasive Candida infection and a constructed reference standard for proven or probable infection. The primary outcome was NPV for exclusion of proven Candida infection; we also reported sensitivity, specificity, and likelihood ratios. FINDINGS: Among 4005 patients screened, 1251 were enrolled. A total of 1225 participants, recruited between April, 2018 and Feb, 2023, were evaluable, among whom 54 (4·4%) had proven invasive Candida infection. The median duration of antifungal treatment was 9 days (IQR 5-15), and survival at 28 days was 76·8%. The index tests had similar NPVs: 96·6% (95·3-97·6) for Fungiplex, 97·1% (94·7-98·6) for T2Candida, 96·7% (95·4-97·8) for CandID, and 97·2% (95·5-98·4) for Fungitell; however, sensitivity varied widely among the tests, from 27·5% to 68·6%. The optimal test combination was Fungitell and CandID, which had an NPV of 97·5% (95·7-98·7) and a sensitivity of 75·0%. Combining these biomarkers with standard-of-care blood culture testing further increased the NPV to 98·6% (97·0-99·4), with a sensitivity of 85·1%. INTERPRETATION: No single biomarker had sufficiently high sensitivity to justify stopping empirical antifungal treatment. Combining Fungitell and CandID with standard-of-care blood culture testing could provide a sufficiently high NPV to allow early cessation of empirical antifungal treatment in this patient group, thereby reducing overtreatment, although this gain in sensitivity is accompanied by a reduction in specificity. Randomised trials are needed to confirm the clinical and cost-effectiveness of this diagnostic strategy before it is adopted in practice. FUNDING: UK National Institute for Health and Care Research Health Technology Assessment Programme and the Research Charitable Trust Fund of the Belfast Health & Social Care Trust.

Abstract as published, via PubMed.